The purpose of this project is to study host genetic determinants of infection of inbred mice by murine leukemia viruses (MuLVs), emphasizing the genetically controlled elements affecting induction of MAIDS by replication defective BM5def MuLV. In the case of MAIDS, strain differences in susceptibility reflect the function of host genes that lie both within and outside the MHC complex and control spread of helper virus and/or the activity of the BM5def genome itself. As determined by infection of Fv-1b mouse strains, whose cells are permissive for the B- tropic helper viruses in LP-BM5 MuLV, the H-2 haplotypes b, p and s were among the most sensitive to MAIDS while haplotypes a and d were highly resistant. In H-2d mice, resistance was mapped to the D end of H-2 but this association was inconsistently detected, depending on the background strain. Expression of the MHC Class I I-region Ea gene product has now been shown to modify Class II effects, based on patterns of sensitivity in H-2 recombinant strains and the finding that C57BL/6 transgenic for Ead are much more resistant to MAIDS than the parental mice. Class I- modified resistance does not appear to reflect the suppression of helper virus seen in some resistant strains. In Fv-1n strains, studied by infection with BM5def pseudotyped by N-tropic amphotropic MuLV, development of MAIDS is closely linked to H-2 (haplotypes b and p are sensitive) and to permissiveness of adults to amphotropic virus. In a few strains, however, non-MHC effects can be seen in several instances of delayed disease induction. Spontaneous lymphoid tumors in NFS mice congenic for ecotropic virus induction loci have been used in studies of the correlation of diagnostic outcomes of analysis by histopathology, FACS profiles, immunocytochemistry and molecular probing for Ig and TCR rearrangements.